It is well known that stressful life events can influence the course of disease. There are a number of reports of a higher incidence of infectious disease, autoimmune disease, and malignancies in patients experiencing stressful events. However, the immunologic alterations induced by a stressor and the factors which mediate the relationship between stressful experiences and disease have not been well-characterized. The overall objective of the research is to elucidate those immunologic alterations and isolate the mediating factors. The first aim of the research is to use in vitro techniques to determine: (1) how lymphocytes, NK cells, and accessory cells are affected by a short-term exposure to a stressor; (2) the duration of the immunologic alteration produced by the stressor; (3) whether substances in the plasma or factors derived from mononuclear cells are responsible for the stress- induced alteration; (4) whether hormone producing tissues are responsible for the alteration. The research will be conducted using Lewis rats as the experimental subjects and electric shock as the stressor. Our preliminary results indicate that a short- term exposure to electric shock produces a decreased reactivity of spleen and whole blood lymphocytes to Concanavalin A. Continuation of stressor exposure to an intermediate level resulted in normal spleen cell reactivity to Con-A; however, the decreased reactivity of the spleen cells recurred following long- term stressor exposure. The second aim is to characterize those immunologic changes that result from exposure to an intermediate and long-term stressor. Special consideration will be given to the differential effects observed in spleen and blood lymphocytes with increasing amounts of stressor exposure. The final aim is to make direct assessments of the effect of stressor exposure on immune function by performing in vivo studies. These studies will evaluate the effect of exposure to a short-, intermediate-, and long-term stressor on immune function by using an immunization model. The plan is to assess the immunization response to sheep erythrocytes (that response requires T helper cell interaction), polyvinylpyroloidone (PVP, a direct stimulator of B lymphocytes), and candida (a fungus associated with a number of immunologic defects). The significance of the research is viewed not only in terms of enhanced knowledge of the stress-induced alterations in immune function and the related health benefits, but also in terms of providing a well-defined immunologic basis for additional studies examining the psychological aspects of stress.